Changes In Low-density Lipoprotein Research Articles

Interferon-free hepatitis C treatment increases a surrogate of atherosclerotic cardiovascular disease risk in Black veterans living with HIV.

Veterans living with HIV (VLWH) and hepatitis C virus (HCV) co-infection have an exacerbated risk of cardiovascular disease (CVD). It is unknown if HCV cure reduces CVD risk in this population. We evaluated changes in low-density lipoprotein (LDL), as a surrogate of CVD risk, 18 months after HCV cure in VLWH. We found significant increases in LDL in VLWH with advanced fibrosis, potentially increasing CVD risk. Lower LDL thresholds to initiate lipid-lowering therapies in VLWH after HCV cure may be warranted.

Inclisiran in individuals with diabetes or obesity: Post hoc pooled analyses of the ORION-9, ORION-10 and ORION-11 Phase 3 randomized trials.

To conduct a pooled analysis of Phase 3 trials investigating the efficacy and safety of inclisiran across glycaemic and body mass index (BMI) strata. Participants were randomized 1:1 to receive 300 mg inclisiran sodium or placebo twice yearly, after initial and 3-month doses up to 18 months, with background oral lipid-lowering therapy. Analyses were stratified by glycaemic status (normoglycaemia, prediabetes, and diabetes) or BMI (<25, ≥25 to <30, ≥30 to <35, and ≥35 kg/m2). Co-primary endpoints were percentage and time-adjusted percentage change in low-density lipoprotein (LDL) cholesterol from baseline. Safety was also assessed. Baseline characteristics were balanced between treatment arms and across strata. Percent LDL cholesterol change (placebo-corrected) with inclisiran from baseline to Day 510 ranged from -47.6% to -51.9% and from -48.8% to -54.4% across glycaemic/BMI strata, respectively. Similarly, time-adjusted percentage changes after Day 90 and up to Day 540 ranged from -46.8% to -52.0% and from -48.6% to -53.3% across glycaemic/BMI strata, respectively. Inclisiran led to significant reductions in proprotein convertase subtilisin/kexin type 9 and other atherogenic lipids and lipoproteins versus placebo across the glycaemic/BMI strata. The proportions of individuals achieving LDL cholesterol thresholds of <1.8 mmol/L and <1.4 mmol/L with inclisiran increased with increasing glycaemic and BMI strata. Across the glycaemic/BMI strata, a higher proportion of individuals had mild/moderate treatment-emergent adverse events (TEAEs) at the injection site with inclisiran (2.8%-7.7%) versus placebo (0.2%-2.1%). Inclisiran provided substantial and sustained LDL cholesterol lowering across glycaemic/BMI strata, with a modest excess of transient mild-to-moderate TEAEs at the injection site.

Impact of a Quality Improvement Initiative on Medical Management of Veterans With Peripheral Artery Disease

Guideline-directed medical therapy (GDMT) for peripheral artery disease (PAD) remains severely underused. Prevention of Amputation in Veterans Everywhere (PAVE) is a screening program designed to prevent or delay major lower extremity amputation. This study aimed to determine whether diagnosis of PAD through the PAVE program improves the prescription of GDMT in veterans with asymptomatic PAD. Patients enrolled into the PAVE program from our institution from 2020 to 2021 were included. Patients with an abnormal ankle-brachial index (ABI), defined as ABI <0.9 or >1.2, were selected for further analysis. Primary outcome was adherence to GDMT, following class I and class IIa recommendations. Secondary outcomes included changes in low-density lipoprotein (LDL), blood pressure, and hemoglobin A1c (HbA1c). A total of 6,313 patients were enrolled into the PAVE program between 2020 and 2021. Of these, 211 had abnormal ABI and were included in our analysis. With enrollment into PAVE, there was significant increase in the prescription of aspirin (74.4% vs 64.9%, p = 0.044) and statins (91.5% vs 82%, p = 0.006). The overall adherence to GDMT significantly increased (56.9% vs 38.9%, p <0.001). The number of patients needed to enroll in PAVE to improve GDMT adherence is 5.6 (95% confidence interval 3.6 to 12.3). Patients enrolled into PAVE program saw significant decreases in HbA1c, with mean decrease of 0.3 (p = 0.012) and a decrease in LDL, with a mean decrease of 6.2 (p = 0.01). In conclusion, enrollment into an amputation prevention program secondarily increased adherence to GDMT, driven by increases in the prescription of statins and aspirin, with resulting decreases in HbA1c and LDL.

Serum Metabolomic Profiling of Patients with Lipedema.

Lipedema is a chronic condition characterized by disproportionate and symmetrical enlargement of adipose tissue, predominantly affecting the lower limbs of women. This study investigated the use of metabolomics in lipedema research, with the objective of identifying complex metabolic disturbances and potential biomarkers for early detection, prognosis, and treatment strategies. The study group (n = 25) comprised women diagnosed with lipedema. The controls were 25 lean women and 25 obese females, both matched for age. In the patients with lipedema, there were notable changes in the metabolite parameters. Specifically, lower levels of histidine and phenylalanine were observed, whereas pyruvic acid was elevated compared with the weight controls. The receiver operating characteristic (ROC) curves for the diagnostic accuracy of histidine, phenylalanine, and pyruvic acid concentrations in distinguishing between patients with lipedema and those with obesity but without lipedema revealed good diagnostic ability for all parameters, with pyruvic acid being the most promising (area under the curve (AUC): 0.9992). Subgroup analysis within matched body mass index (BMI) ranges (30.0 to 39.9 kg/m2) further revealed that differences in pyruvic acid, phenylalanine, and histidine levels are likely linked to lipedema pathology rather than BMI variations. Changes in low-density lipoprotein (LDL)-6 TG levels and significant reductions in various LDL-2-carried lipids of patients with lipedema, compared with the lean controls, were observed. However, these lipids were similar between the lipedema patients and the obese controls, suggesting that these alterations are related to adiposity. Metabolomics is a valuable tool for investigating lipedema, offering a comprehensive view of metabolic changes and insights into lipedema's underlying mechanisms.

Healthy grocery delivery in the usual care for adults recovering from an acute coronary event: protocol for a three-arm randomised controlled trial

IntroductionCoronary heart disease is a major contributor to the global burden of disease. Appropriate nutrition is a cornerstone of the prevention and treatment of coronary heart disease; however, barriers including...

Transiently impaired endothelial function during thyroid hormone withdrawal in differentiated thyroid cancer patients.

Endothelial dysfunction, which was associated with chronic hypothyroidism, was an early event in atherosclerosis. Whether short-term hypothyroidism following thyroxine withdrawal during radioiodine (RAI) therapy was associated with endothelial dysfunction in patients with differentiated thyroid cancer (DTC) was unclear. Aim of the study was to assess whether short-term hypothyroidism could impair endothelial function and the accompanied metabolic changes in the whole process of RAI therapy. We recruited fifty-one patients who underwent total thyroidectomy surgery and would accept RAI therapy for DTC. We analyzed thyroid function, endothelial function and serum lipids levels of the patients at three time points: the day before thyroxine withdrawal(P1), the day before 131I administration(P2) and 4-6 weeks after RAI therapy(P3). A high-resolution ultrasound named flow-mediated dilation (FMD) was used to measure endothelial function of the patients. We analyzed the changes of FMD, thyroid function and lipids at three time points. FMD(P2) decreased significantly compared to FMD(P1) (P1vsP2, 8.05 ± 1.55vs 7.26 ± 1.50, p<0.001). There was no significant difference between FMD(P3) and FMD(P1) after restoring TSH (thyroid stimulating hormone) suppression therapy (P1 vs P3, 8.05 ± 1.55 vs 7.79 ± 1.38, p=0.146). Among all parameters, the change of low-density lipoprotein (ΔLDL) was the only factor correlated negatively with the change of FMD (ΔFMD) throughout the RAI therapy process (P1-2, r=-0.326, p=0.020; P2-3, r=-0.306, p=0.029). Endothelial function was transiently impaired in DTC patients at short-term hypothyroidism state during the RAI therapy, and immediately returned to the initial state after restoring TSH suppression therapy.

The indirect impact of the COVID-19 pandemic on people with type 2 diabetes mellitus and without COVID-19 infection: Systematic review and meta-analysis

BackgroundThe effect directly from the coronavirus disease 2019 (COVID-19) infection on health and fatality has received considerable attention, particularly among people with type 2 diabetes mellitus (T2DM). However, evidence on the indirect impact of disrupted healthcare services during the pandemic on people with T2DM is limited. This systematic review aims to assess the indirect impact of the pandemic on the metabolic management of T2DM people without a history of COVID-19 infection. MethodsPubMed, Web of Science, and Scopus were systematically searched for studies that compared diabetes-related health outcomes between pre-pandemic and during-pandemic periods in people with T2DM and without the COVID-19 infection and published from January 1, 2020, to July 13, 2022. A meta-analysis was performed to estimate the overall effect on the diabetes indicators, including hemoglobin A1c (HbA1c), lipid profiles, and weight control, with different effect models according to the heterogeneity. ResultsEleven observational studies were included in the final review. No significant changes in HbA1c levels [weighted mean difference (WMD), 0.06 (95% CI −0.12 to 0.24)] and body weight index (BMI) [0.15 (95% CI −0.24 to 0.53)] between the pre-pandemic and during-pandemic were found in the meta-analysis. Four studies reported lipid indicators; most reported insignificant changes in low-density lipoprotein (LDL, n = 2) and high-density lipoprotein (HDL, n = 3); two studies reported an increase in total cholesterol and triglyceride. ConclusionsThis review did not find significant changes in HbA1c and BMI among people with T2DM after data pooling, but a possible worsening in lipids parameters during the COVID-19 pandemic. There were limited data on long-term outcomes and healthcare utilization, which warrants further research. Systematic review registrationPROSPERO CRD42022360433.

Desidustat in Anemia due to Non-Dialysis-Dependent Chronic Kidney Disease: A Phase 3 Study (DREAM-ND)

Background: Desidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, is being developed to treat anemia in patients with chronic kidney disease (CKD) without dialysis dependency. Methods: In total, 588 patients with a clinical diagnosis of anemia due to CKD without dialysis need and with baseline hemoglobin of 7.0–10.0 g/dL (inclusive) were randomized in a 1:1 ratio to receive either desidustat 100 mg oral tablets thrice a week for 24 weeks or biosimilar darbepoetin subcutaneous injection 0.75 μg/kg once in 2 weeks for 24 weeks. The primary outcome was the change from baseline in hemoglobin to evaluation period of Weeks 16–24. Key secondary outcomes included the number of patients with hemoglobin response, changes in the hepcidin levels, changes in the vascular endothelial growth factor (VEGF) levels, and changes in the lipid and lipoprotein profiles. Results: Hemoglobin change from baseline to Weeks 16–24 was 1.95 g/dL in the desidustat group and 1.83 g/dL in the darbepoetin group (difference: 0.11 g/dL; 95% CI: −0.12, 0.34), which met prespecified non-inferiority margin (−0.75 g/dL). The hemoglobin responders were significantly higher (p = 0.0181) in the desidustat group (196 [77.78%]) compared to the darbepoetin group (176 [68.48%]). The difference of change in hepcidin from baseline to Week 12 and Week 24 (p = 0.0032 at Week 12, p = 0.0016 at Week 24) and the difference of change in low-density lipoprotein from baseline to Week 24 (p value = 0.0269) between the two groups was statistically significant. The difference of change from baseline in VEGF to Weeks 12 and 24 between the two groups was not statistically significant. Conclusion: Desidustat is non-inferior to darbepoetin in the treatment of anemia due to non-dialysis dependent CKD and it is well-tolerated.

Biochemical evaluation of DPP4 inhibitors on lipid profile in type 2 diabetes mellitus patients: A hospital-based prospective study

Background: Lipid lowering action of oral hypoglycemic drugs is still unclear. Hence, this study was conducted to address the same using monotherapy and with combination of oral hypoglycemic in patients suffering with type 2 diabetes. Aims and Objectives: The main aim and objective of the study was to evaluate the DPP4 inhibitors inducted changes in low-density lipoprotein (LDL), VLSL, high-density lipoprotein (HDL), and total cholesterol (TC) in patients suffering with type 2 diabetes. Materials and Methods: This randomized control study was done in the Department of General Medicine, Chennai Medical College Hospital and Research Center, Irungalur, Tiruchirappalli, between June 2014 and July 2015. Cases with type 2 diabetes mellitus (T2DM) aged 30–70 years who had been on glibenclamide or metformin for the past 3 months and had uncontrolled blood glucose levels were selected for the study. Total 180 patients are fulfilling the inclusion and exclusion criteria were divided into six groups (Each with 30 patients.) At the 0th and 12th weeks, fasting lipid profile was assessed. The data were expressed in number, percentage, mean, and standard deviation. Results: Oral hypoglycemic drug either as monotherapy or in combination has significant effect on lipid profile among the cases with T2DM. Furthermore, the significant decrease in TC and maximum improvement in HDL was noted with the use of glibenclamide in combination with Sitagliptin and maximum reduction in triglycerides and LDL was noted with the use of Metformin in combination with Sitagliptin. Conclusion: Oral hypoglycemic agents have an additional favorable effect on lipid profile among the cases with T2DM.

Abstract 10469: Cardiometabolic Risk Factors as Causal Mediators of the Relationship Between High Body Mass Index and Chronic Kidney Disease: A Two-Step Mendelian Randomization Study and Mediation Analyses

Introduction: Observational studies suggest that obesity is a risk factor of chronic kidney disease (CKD). It is unclear whether this reflects a direct causal effect of obesity or an effect mediated by obesity-related metabolic changes. Hypotheses: We hypothesised that 1) obesity is a causal risk factor of CKD defined as eGFR &lt;60mL/min/1.73m 2 and 2) this causal effect is mediated through changes in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterols, triglycerides, glucose, blood pressure and C-reactive protein (CRP) levels. Methods: To assess causality and investigate mediation, we used a combination of observational, two-step Mendelian randomization, and mediation analyses on individual-level data from two cohorts of the Danish general population (N=117,213). Results: Observationally, higher BMI was associated with a lower eGFR (change in eGFR; -0.81, confidence interval [CI]: -0.89- -0.73)) and a higher risk of CKD (odds ratio [OR]:1.19; 95% CI: 1.16-1.22) per 5kg/m 2 higher BMI (p for trend for both &lt;2.9 x10 -40 ). Mendelian randomization analyses supported a causal effect of higher BMI on lower eGFR (change in eGFR -17.3 mL/min/1.73m 2 (95%CI: -19.3- -15.3), and risk of CKD (risk ratio [RR]6.99 (95%CI: 1.63-30.1) per 5kg/m 2 higher BMI. Measured BMI and the BMI allele score used in Mendelian randomization analyses were associated with changes in levels of LDL and HDL cholesterols, triglycerides, glucose, blood pressure, and CRP. Observational and Mendelian randomization analyses showed evidence to support a causal effect of changes in levels of systolic and diastolic blood pressure, LDL cholesterol and CRP with lower eGFR and higher risk of CKD. Of the excess risk of CKD coming from high BMI, elevated systolic and diastolic blood pressure mediated 18%(95%CI:14-22) and 9% (7-11), respectively. 9% (95%CI: 8-12) was mediated by elevated LDL cholesterol and 29% (95%CI: 23-35) by elevated CRP. Conclusion: Triangulating evidence from observational and Mendelian randomization analyses provided evidence to support a causal role of obesity on the risk of CKD and that this causal effect may be partly mediated by elevated systolic and diastolic blood pressure, CRP and LDL cholesterol levels.

Effect of sofosbuvir-based DAAs on changes in lower-density lipoprotein in HCV patients: a systematic review and meta-analysis

BackgroundPrevious studies reported worsened lipid profiles in patients infected with hepatitis C virus (HCV) during direct-acting antivirals (DAAs) treatment. This study aimed to investigate the effect of sofosbuvir (SOF)-based DAAs on changes in low-density lipoprotein (LDL) in HCV patients.MethodsA systematic review of articles published before 31 May 2021 was conducted by searching MEDLINE, Cochrane Library, EMBASE, and CINAHL Plus. Eligible studies were those comparing SOF-based DAAs and non-SOF DAAs for HCV patients and providing numerical data for changes in LDL. Risk of Bias in Non-randomized Studies- of Interventions was used for assessing risk of bias, and meta-analysis was performed for changes in LDL.ResultsSix studies comprising 1248 patients were included, 848 patients treated with SOF-based DAAs and 400 patients with non-SOF DAAs vs. SOF-based DAAs group had significantly greater increases in LDL from baseline to week 4 than non-SOF DAAs group (P = 0.001). However, changes in LDL from baseline to the end of treatment (P = 0.060), to post-treatment week 12 (P = 0.263), and to post-treatment week 24 (P = 0.319) did not significantly differ between the two groups. Further comparison of SOF/ledipasvir with asunaprevir/daclatasvir revealed a similar trend in changes in LDL.ConclusionsFor HCV patients, SOF-based DAA regimens were associated with rapid and significant increases in LDL during the initial 4 weeks of treatment, and the changes did not sustain after the end of treatment. Potential mechanism might be related to the phosphoramidate side chain of SOF.

Roxadustat for the treatment of anaemia in chronic kidney disease patients not on dialysis: a Phase 3, randomized, open-label, active-controlled study (DOLOMITES).

BackgroundRoxadustat, an orally administered hypoxia-inducible factor prolyl hydroxylase inhibitor, is being evaluated for treatment of anaemia of chronic kidney disease (CKD).MethodsThis randomized, open-label, active-controlled Phase 3 study compared roxadustat versus darbepoetin alfa (DA) in non-dialysis-dependent (NDD) CKD patients with anaemia for ≤104 weeks. Doses were titrated to correct and maintain haemoglobin (Hb) within 10.0–12.0 g/dL. The primary endpoint was Hb response in the full analysis set, defined as Hb ≥11.0 g/dL and Hb change from baseline (BL; CFB) ≥1.0 g/dL in patients with BL Hb >8.0 g/dL or CFB ≥2.0 g/dL in patients with BL Hb ≤8.0 g/dL during the first 24 weeks of treatment without rescue therapy (non-inferiority margin, −15%). Key secondary endpoints included change in low-density lipoprotein (LDL), time to first intravenous (IV) iron use, change in mean arterial pressure (MAP) and time to hypertension occurrence. Adverse events were assessed.ResultsOf 616 randomized patients (roxadustat, 323; DA, 293), 424 completed treatment (roxadustat, 215; DA, 209). Hb response with roxadustat was non-inferior to DA (roxadustat: 256/286, 89.5% versus DA: 213/273, 78.0%, difference 11.51%, 95% confidence interval 5.66–17.36%). Roxadustat maintained Hb for up to 2 years. Roxadustat was non-inferior to DA for change in MAP and time to occurrence of hypertension and superior for change in LDL and time to first IV iron use. Safety profiles were comparable between groups. Findings suggest that there was no difference between groups regarding the composite endpoints major adverse cardiovascular events (MACEs) and MACE+ [MACE: 0.81 (0.52–1.25), P = 0.339; MACE+: 0.90 (0.61–1.32), P = 0.583].ConclusionsRoxadustat is a viable option to treat anaemia in NDD CKD patients maintaining Hb levels for up to 104 weeks.

Metabolic Properties of Lowdensity Lipoprotein (LDL) Triglycerides in Patients with Type 2 Diabetes, Comparison with Small Dense LDL-Cholesterol.

Aims: Abnormal compositional changes in low-density lipoprotein (LDL) particles, such as triglyceride (TG) enrichment and size reduction, are common in patients with diabetes. Several cohort studies have demonstrated that LDL-TG and sdLDL-cholesterol (C) are sensitive biomarkers for predicting atherosclerotic cardiovascular diseases beyond LDL-C. Although sdLDL has been extensively studied, little is known about the properties of LDL-TG. We investigated similarities or differences between LDL-TG and sdLDL-C. Methods: Fasting plasma was obtained from 1,085 patients with type 2 diabetes who were enrolled in the diabetes regional cohort study (ViNA Cohort). LDL-TG and sdLDL-C concentrations were measured using a homogeneous assay established by us. In a subset of subjects, LDL-TG and sdLDL-C levels were measured postprandially or after treatment with lipid-lowering drugs. Results: In a quartile analysis, higher LDL-TG quartiles were associated with higher frequency of female and fibrate users, whereas sdLDL-C quartiles were associated with frequency of men, drinking, and metabolic syndrome-related measurements. Higher quartiles of LDL-TG/LDL-C were associated with smoking, drinking, fibrate users, and statin users. LDL-TG was significantly correlated with TG, LDL-C, sdLDL-C, and apolipoprotein (apo) B, with apoB being the primary determinant. LDL-TG correlated to high sensitive C-reactive protein (CRP) independently of other lipids. Mean LDL-TG did not change with fasting/non-fasting. Statin treatment reduced LDL-TG, whereas fibrates increased it, but these drugs reduced sdLDL-C equally. Conclusions: LDL-TG levels were more tightly regulated by the number of LDL particles than plasma TG levels were. SdLDL-C was closely associated with metabolic syndrome-related factors, whereas LDL-TG was associated with low-grade systemic inflammation.

Effectiveness of Consumption of a Combination of Citrus Fruit Flavonoids and Olive Leaf Polyphenols to Reduce Oxidation of Low-Density Lipoprotein in Treatment-Naïve Cardiovascular Risk Subjects: A Randomized Double-Blind Controlled Study.

The aim of the study was to assess whether oral intake of a nutraceutical product (Citrolive™) could determine changes in low-density lipoprotein (LDL) oxidation and other parameters of lipid metabolism and plasma atherogenic capacity. Citrolive™ is a commercial extract obtained from the combination of citrus fruit flavonoids and olive leaf extracts. Twenty-three untreated subjects (69.6% males, 30.4% females, mean age 41.9 ± 9.4 years) with cardiovascular risk factors and a total cholesterol level >200 mg/dL and LDL cholesterol (LDL-C) > 130 mg/dL participated in a 3-month randomized double-blind controlled study. Participants in the intervention group (71.4% males, 28.6% females, mean age 42.7 ± 9.7 years) consumed Citrolive™ (500 mg, two capsules/day), and controls (66.7% males, 33.3% females, mean age 40.6 ± 9.4 years) received a matched placebo. At 3 months, oxidized LDL (ox-LDL) decreased significantly in the intervention group from 93.8 ± 19.1 U/L to 62.8 ± 28.7 U/L (p < 0.05), whereas the control group increased from 98.2 ± 23.5 U/L to 105.7 ± 21.9 U/L (p = 0.1). Between-group differences were also significant (p < 0.05). Similar findings in the ox-LDL/LDL-C ratio were observed. Serum paraoxonase activity (PON1) increased significantly in the intervention group from 64.5 ± 15.6 U/L to 78.7 ± 28.8 U/L (p < 0.05) but remained unchanged in controls. Consumption of Citrolive™ for 3 months in treatment-naïve subjects with moderate risk of atherosclerosis was associated with a reduction in oxidized LDL-C and LDL-oxidase/LDL-C ratio as compared to controls.

Features of infrared spectra of blood plasma of patients with dyslipidemia

The paper analyzes the IR spectra of blood plasma from healthy donors, patients with brain infarction and patients with coronary heart disease (CHD). It was found that the structure of the main transport protein of blood plasma – albumin – in the blood plasma of patients with brain infarction, patients with CHD and representatives of the control group is almost identical. It is shown that in the absence of changes in the secondary and tertiary structure of albumin, the increase in binding of anionic hydrophobic metabolites in the blood plasma of patients with dyslipidemia compared to control is due to structural changes in low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL).

A Comparison of Effectiveness of Crystalline and Amorphous Atorvastatin

Background: Atorvastatin is a widely used statin, of which there are two available polymorphs: crystalline (original) and amorphous (generic). Pharmacological studies showed the similarity between both forms. However, the lipid-lowering effectiveness of the amorphous form was still uncertain. Objective: To compare the effectiveness of crystalline and amorphous form of atorvastatin. Materials and Methods: The authors conducted an observational cross-sectional analytic study by retrospectively collecting data from January 1, 2016 to December 31, 2017 of the patients at Queen Sirikit Heart Center of the Northeast where the original regimen of crystalline atorvastatin had been replaced by the amorphous atorvastatin at the same dose. Patients must have been prescribed each form of atorvastatin for at least six weeks. The lipid profiles taken at the closest to the switching point (before and after) were used. The primary outcome was changes in low-density lipoprotein (LDL) levels. The secondary outcomes were changes in total cholesterol (TC), triglyceride (TG), and high-density lipoprotein (HDL) levels, as well as a comparison of LDL levels in patients whose tablets were split. Results: Eight hundred twenty-five patients were included in the present study. The mean age was 63.7±9.9 years. Five hundred sixty-eight patients (68.8%) were male, and 736 (89.2%) were treated as secondary prevention. The mean LDL levels during crystalline and amorphous atorvastatin use were 92.4±39.0 and 91.8±41.0 mg/dL, respectively (mean difference –0.6; 95% confidence interval [CI], –2.2 to 1.0; p=0.460). The mean TC, TG, and HDL levels during crystalline and amorphous form use were 153.1±43.3 and 152.0±48.6 mg/dL (p=0.400), 153.4±129.0 and 155.0±148.3 (p=0.740), 43.6±11.9, and 44.4±12.0 (p=0.004), respectively. Among the patients who had tablet splitting, the mean LDL levels during crystalline and amorphous atorvastatin use were 89.2±28.3 and 91.0±30.8 mg/dL, respectively (p=0.279). Side effects were recorded in nine patients, one of which was rhabdomyolysis. Conclusion: The effectiveness of amorphous atorvastatin at lowering lipids was comparable to that of atorvastatin in its crystalline form, and patients were generally able to tolerate amorphous atorvastatin. Keywords: Atorvastatin, Crystalline, Amorphous, Lipid-lowering, Low-density lipoprotein

Unwanted Hormonal and Metabolic Effects of Postoperative Adjuvant Mitotane Treatment for Adrenocortical Cancer.

Simple SummaryMitotane is the only drug approved for treatment of adrenocortical cancer. Although mitotane is a derivative of the pesticide dichlorodiphenyltrichloroethane (DDT), limited data are available on its toxicity. Herein, we reported on the type and frequency of mitotane adverse events and on supportive therapies used to deal with toxicity in 74 mitotane-treated patients. Beyond the expected glucocorticoid insufficiency, a significant number of patients had a deficit of mineralocorticoid hormones, hypothyroid state and impaired testicular function, while fertile women frequently developed ovarian cysts during mitotane treatment. Multiple hormone replacement therapies were needed in >30% of patients. Statins were used in 50% of patients for significant hypercholesterolemia. Supportive therapies were able to revert the biochemical alterations, although higher doses were frequently used due to pharmacokinetic interactions with mitotane. Our study underlines the need of a careful and global approach to manage mitotane toxicity, to make adjuvant therapy safer and easier for patients.Mitotane is widely used for the treatment of adrenocortical cancer (ACC), although the drug-related toxicity complicates its use. The aim of this study is to assess comprehensively the different endocrine and metabolic unwanted effects of the drug, and to provide data on the supportive therapies. We retrospectively analyzed 74 ACC patients adjuvantly treated with mitotane for ≥12 months. During the treatment period (40 months, 12–195), 32.4% of patients needed replacement therapy for mineralocorticoid deficit, 36.2% for hypothyroidism and 34.3% for male hypogonadism. In fertile women, hypogonadism was uncommon, while 65.4% of women developed ovarian cysts. Although no significant change in low-density lipoprotein (LDL) was observed, statins were started in 50% of patients for a significant increase in total cholesterol and triglycerides. Dyslipidemia occurred early, after a median time of 6 months from mitotane start. Conversely, testosterone replacement was usually started after >2 years. In many cases, ranging from 29.4% to 50% according to the side effect, toxicity occurred well before the achievement of the target mitotane concentrations. Supportive therapies were able to revert the biochemical alterations induced by mitotane, although higher doses were needed for a likely pharmacokinetic interaction of exogenous steroids and statins with mitotane. In conclusion, adjuvant mitotane therapy is associated with a spectrum of unwanted effects encompassing the function of different endocrine glands and requires a careful clinical and biochemical assessment associated with the therapeutic drug monitoring.

Effect of Peer Mentors in Diabetes Self-management vs Usual Care on Outcomes in US Veterans With Type 2 Diabetes

Diabetes is a substantial public health issue. Peer mentoring is a low-cost intervention for improving glycemic control in patients with diabetes. However, long-term effects of peer mentoring and creation of sustainable models are not well studied. Assess the effects of a peer support intervention for improving glycemic control in patients with diabetes and evaluate a model in which former mentees serve as mentors. A randomized clinical trial was conducted from September 27, 2012, to March 21, 2018, at the Corporal Michael J. Crescenz Medical Center. US veterans with type 2 diabetes aged 30 to 75 years with hemoglobin A1C (HbA1c) greater than 8% received support over 6 months from peers with prior poor glycemic control but who had achieved HbA1c less than or equal to 7.5% (phase 1). Phase 1 mentees were then randomized to become a mentor or not to new randomly assigned participants in phase 2. Outcomes were assessed at 6 and 12 months. Data were analyzed from October 5, 2016, to September 4, 2018. Mentors who received an initial training session and monthly reinforcement training were assigned 1 mentee and given $20 for each month they contacted their mentee at least weekly. Primary outcome was HbA1c change at 6 months. Secondary outcomes included HbA1c change at 12 months and change in low-density lipoprotein, blood pressure, diabetes quality of life, and depression symptoms at 6 and 12 months. The study enrolled 365 participants into phase 1 and 122 participants into phase 2. Most participants were Black (341 [66%]) and male (454 [96%]), with a mean (SD) age of 60 (7.5) years. Mean phase 1 HbA1c change at 6 months for usual care was -0.20% (95% CI, -0.46% to 0.06%) vs -0.52% (95% CI, -0.76% to -0.29%) for mentees (P = .06). Mean phase 2 HbA1c change at 6 months for usual care was -0.46% (95% CI, -1.02% to 0.10%) vs 0.08% (95% CI, -0.42% to 0.57%) for mentees (P = .16). There were no differences in secondary outcomes or HbA1c levels at 12 months. There was no benefit to past mentees who became mentors. In this randomized clinical trial, a peer mentor intervention did not improve 6-month HbA1c levels and did not have sustained benefits. ClinicalTrials.gov Identifier: NCT01651117.

Heterogeneous Metabolic Response to Exercise Training in Heart Failure with Preserved Ejection Fraction.

The prevalence of heart failure with preserved ejection fraction (HFpEF) is constantly increasing and no evidence-based pharmacological treatment option is available. While exercise training (ET) improves diastolic function, its metabolic mechanisms in HFpEF are unclear. We assessed the metabolic response to 12 weeks of ET in patients with HFpEF by performing a post hoc analysis of the EX-DHF-P trial (ISRCTN86879094). Plasma concentrations of 188 endogenous metabolites were measured in 44 ET and 20 usual care (UC) patients at baseline and 3-months follow-up. Metabolic differences between ET and UC from baseline to follow-up were compared and differential responses to ET were examined by random forest feature selection. ET prevented the increase of acetylornithine and carnitine as well as the decrease of three glycerophospholipids. After ET, two opposite metabolic response clusters were identified. Cluster belonging was associated with perceived well-being at baseline and changes in low-density lipoprotein but not with cardiorespiratory, ventilatory or echocardiographic parameters. These two ET-induced metabolic response patterns illustrate the heterogeneity of the HFpEF patient population. Our results suggest that other biological parameters might be helpful besides clinical variables to improve HFpEF patient stratification. Whether this approach improves response prediction regarding ET and other treatments should be explored.

Changes in blood lipid concentrations associated with changes in intake of dietary saturated fat in the context of a healthy low-carbohydrate weight-loss diet: a secondary analysis of the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) trial

For low-carbohydrate diets, a public health approach has focused on the replacement of carbohydrates with unsaturated fats. However, little research exists on the impacts of saturated fat intake on the lipid profile in the context of whole-food-based low-carbohydrate weight-loss diets. The primary aim of this secondary analysis of the DIETFITS weight loss trial was to evaluate the associations between changes in percentage of dietary saturated fatty acid intake (%SFA) and changes in low-density lipoproteins, high-density lipoproteins, and triglyceride concentrations for those following a healthy low-carbohydrate (HLC) diet. The secondary aim was to examine these associations specifically for HLC dieters who had the highest 12-month increases in %SFA. In the DIETFITS trial, 609 generally healthy adults, aged 18-50 years, with body mass indices of 28-40 kg/m2 were randomly assigned to a healthy low-fat (HLF) or HLC diet for 12 months. In this analysis, linear regression, both without and with adjustment for potential confounders, was used to measure the association between 12-month change in %SFA and blood lipids in 208 HLC participants with complete diet and blood lipid data. Participants consumed an average of 12-18% of calories from SFA. An increase of %SFA, without significant changes in absolute saturated fat intake, over 12 months was associated with a statistically significant decrease in triglycerides in the context of a weight-loss study in which participants simultaneously decreased carbohydrate intake. The association between increase in %SFA and decrease in triglycerides was no longer significant when adjusting for 12-month change in carbohydrate intake, suggesting carbohydrate intake may be a mediator of this relationship. Those on a low-carbohydrate weight-loss diet who increase their percentage intake of dietary saturated fat may improve their overall lipid profile provided they focus on a high-quality diet and lower their intakes of both calories and refined carbohydrates. This trial was registered at clinicaltrials.gov as NCT01826591.